Department of Radiation Oncology, Division of Radiation and Cancer Biology, Stanford University School of Medicine, Stanford, California 94305, USA; email:
Department of Genetics and Stanford Cancer Institute, Stanford University School of Medicine, Stanford, California 94305, USA.
Annu Rev Pathol. 2022 Jan 24;17:205-226. doi: 10.1146/annurev-pathol-042320-025840. Epub 2021 Oct 26.
, encoding the p53 transcription factor, is the most frequently mutated tumor suppressor gene across all human cancer types. While p53 has long been appreciated to induce antiproliferative cell cycle arrest, apoptosis, and senescence programs in response to diverse stress signals, various studies in recent years have revealed additional important functions for p53 that likely also contribute to tumor suppression, including roles in regulating tumor metabolism, ferroptosis, signaling in the tumor microenvironment, and stem cell self-renewal/differentiation. Not only does loss or mutation cause cancer, but hyperactive p53 also drives various pathologies, including developmental phenotypes, premature aging, neurodegeneration, and side effects of cancer therapies. These findings underscore the importance of balanced p53 activity and influence our thinking of how to best develop cancer therapies based on modulating the p53 pathway.
编码 p53 转录因子的基因是所有人类癌症类型中最常发生突变的肿瘤抑制基因。尽管 p53 长期以来一直被认为能够在受到各种应激信号时诱导抗增殖细胞周期停滞、细胞凋亡和衰老程序，但近年来的多项研究揭示了 p53 的其他重要功能，这些功能可能也有助于肿瘤抑制，包括调节肿瘤代谢、铁死亡、肿瘤微环境信号以及干细胞自我更新/分化。不仅 缺失或突变会导致癌症，而且 p53 的过度活跃也会引发各种病理，包括发育表型、过早衰老、神经退行性变和癌症治疗的副作用。这些发现强调了平衡 p53 活性的重要性，并影响了我们关于如何基于调节 p53 途径来开发最佳癌症疗法的思考。
